PERTAIN: An Efficacy and Safety Study of Paliperidone Extended-Release (ER) Tablets in Participants With Schizophrenia

Sponsor
Janssen-Cilag International NV (Industry)
Overall Status
Completed
CT.gov ID
NCT00566631
Collaborator
(none)
294
30
1
22
9.8
0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the tolerability, safety and treatment response of flexible doses of paliperidone extended-release (ER; designed to slowly release a drug in the body over an extended period of time) tablets in participants with acute schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is an open-label (all people know the identity of the intervention), single-arm (getting one dose of medicine), multi-center (conducted in more than 1 center) study to evaluate tolerability, safety and efficacy of flexible daily doses of paliperidone ER in participants with acute schizophrenia. All participants will be given paliperidone ER once daily at a dose of 3, 6, 9, or 12 milligram (mg) tablets orally depending on Investigator's discretion, based on participant's clinical response and tolerability towards paliperidone ER. The duration of the core phase of the treatment will be 6 weeks and the participants who will complete this phase, respond well and would like to continue, will be eligible to be enrolled in an extension phase, which is no longer than 12 months. Efficacy will primarily be evaluated by treatment response evaluated through total Positive and Negative Syndrome Scale (PANSS) score. Participants' safety will be monitored throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
294 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Tolerability, Safety and Treatment Response of Flexible Doses of Paliperidone ER in Acutely Exacerbated Subjects With Schizophrenia
Study Start Date :
Jul 1, 2007
Actual Primary Completion Date :
May 1, 2008
Actual Study Completion Date :
May 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Paliperidone Extended Release (ER)

Drug: Paliperidone
Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion will be given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
Other Names:
  • Invega
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment Response Based on Total PANSS Scale Score [Day 42 or early discontinuation]

      Response was defined as decrease of at least 30 percent in total Positive and Negative Syndrome Scale (PANSS) score from Baseline to endpoint of core phase (which is, Day 42 or early discontinuation). The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, & poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of sum of all 30 PANSS items & ranges from 30 to 210. Higher scores indicate worsening.

    Secondary Outcome Measures

    1. Change From Baseline in Total Positive and Negative Symptom Scale (PANSS) Score at Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.

    2. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Day 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 42 and Final Evaluation (Day 42 or early discontinuation)]

      The PANSS is a 30-item scale to assess neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms and disorganized thoughts subscale, consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement (H/E) subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher score indicates greater severity. Final evaluation is the last post-baseline visit with data.

    3. Percentage of Participants With Treatment Response Greater Than (>) 20 Percent, 40 Percent and 50 Percent in Total Positive and Negative Syndrome Scale (PANSS) Score [Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.

    4. Change From Baseline in Clinical Global Impression -Severity (CGI-S) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "normal, not at all ill" and a rating of 7 is equivalent to "among the most extremely ill participants". Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.

    5. Change From Baseline in Personal and Social Performance Scale (PSP) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The PSP assesses the degree of dysfunction within 4 domains of behavior: socially useful activities, personal & social relationships, self-care & disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 6, very severe) in each of 4 domains. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Final evaluation is the last post-baseline visit with data.

    6. Change From Baseline in Quality of Sleep Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The sleep evaluation scale is a self-administered scale that rates quality of sleep. Participants indicate on an 11-point scale that how well they have slept within the previous 7 days, score ranged from 0 (very badly) to 10 (very well). Final evaluation is the last post-baseline visit with data.

    7. Change From Baseline in Day Time Drowsiness Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The day time drowsiness evaluation scale is a self-administered scale that rates day time drowsiness. Participants indicate on an 11-point scale that how often they have felt drowsy within the previous 7 days, score ranged from 0 (not at all) to 10 (all the time). Final evaluation is the last post-baseline visit with data.

    8. Number of Participants Satisfied With the Study Treatment [Day 42 or early discontinuation]

      Treatment satisfaction with paliperidone ER was assessed by the Investigator and participant on a 5-point scale: 1 (very good), 2 (good), 3 (reasonable), 4 (moderate) and 5 (poor), at the end of the core treatment phase (which is, Day 42 or early discontinuation) by conducting an interview.

    Other Outcome Measures

    1. Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The AIMS is a 12-item scale to provide a numeric measure to the observed abnormal movements in different parts of the body. Information is collected after a brief neurological examination and is scored on a 5-point scale (0=none and 4=severe). Final evaluation is the last post-baseline visit with data.

    2. Change From Baseline in Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The SAS is a 10-item scale used to measure the symptoms of parkinsonism (slow movements) or parkinsonian side-effects related to the use of antipsychotic medications. The SAS rates 10 items (including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, Glabella tap, tremor and salivation), score ranging from 0 (normal) to 4 (extreme). The SAS global score is the average score (total sum of items score divided by the number of items) and ranges between 0 and 4, where the higher score indicates more severe condition of Extrapyramidal Symptoms. Final evaluation is the last post- baseline visit with data.

    3. Change From Baseline in Global Rating Sub-scale Score Based on Barnes Akathisia Rating Scale (BARS) at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation) [Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)]

      The BARS included an objective rating (from 0=normal to 3=constantly engaged), two subjective ratings of symptoms of akathisia, namely awareness of restlessness (ranging from 0=absence of inner restlessness to 3=awareness of intense compulsion to move) and reported distress related to restlessness (ranging from 0=no distress to 3=severe), and a global clinical rating of akathisia, ranging from 0 (absent) to 5 (severe). Global rating sub-scale score (that is, global clinical rating of akathisia) was assessed which was scored separately and is the most relevant measure of severity of akathisia. Higher scores indicates worsening akathisia. Final evaluation is the last post-baseline visit with data.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia

    • Must be experiencing an acute schizophrenic episode with a Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal to 70 at Baseline

    • Must be admitted to hospital for treatment of the acute schizophrenic episode and must agree for voluntary hospitalization for at least the first 7 days of the study

    • Female participants must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (example, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study and female participants of child-bearing potential must have a negative urine pregnancy test at Screening

    • Participants or their legally acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

    Exclusion Criteria:
    • Pregnant or breast-feeding female participants

    • First antipsychotic treatment ever

    • Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment and on clozapine or a long-acting injectable antipsychotic during the last 3 months

    • Known hypersensitivity to paliperidone extended-release (ER) or risperidone

    • Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome including recent or present clinically relevant laboratory abnormalities (as deemed by the Investigator) and participants with current or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Zagreb Croatia
    2 Dieppe N/A France
    3 La Charite Sur Loire France
    4 Metz Cedex 01 France
    5 Augsburg Germany
    6 Bonn Germany
    7 Mainz Germany
    8 Mannheim Germany
    9 München Germany
    10 Rostock Germany
    11 Wasserburg Germany
    12 Be-Er Ya-Acov Israel
    13 Beer Sheva Israel
    14 Hod-Hasharon Israel
    15 Pardesia Israel
    16 Ramat Gan Israel
    17 Klaipeda Lithuania
    18 Siauliai Lithuania
    19 Vilnius Lithuania
    20 Gda Sk Poland Poland
    21 Lubliniec Poland
    22 Lublin Poland
    23 Skape Poland
    24 Swiecie Poland
    25 Torun N/A Poland
    26 Zabki Poland
    27 Łódź Poland
    28 Bucharest Romania
    29 Cluj-Napoca Romania
    30 Craiova Romania

    Sponsors and Collaborators

    • Janssen-Cilag International NV

    Investigators

    • Study Director: Janssen-Cilag International NV, Belgium Clinical Trial, Janssen-Cilag International NV

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Janssen-Cilag International NV
    ClinicalTrials.gov Identifier:
    NCT00566631
    Other Study ID Numbers:
    • CR013162
    • R076477SCH3018
    First Posted:
    Dec 3, 2007
    Last Update Posted:
    Aug 2, 2013
    Last Verified:
    Jun 1, 2013
    Keywords provided by Janssen-Cilag International NV
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Period Title: Part 1: Core Treatment Phase
    STARTED 294
    COMPLETED 234
    NOT COMPLETED 60
    Period Title: Part 1: Core Treatment Phase
    STARTED 234
    COMPLETED 139
    NOT COMPLETED 95
    Period Title: Part 1: Core Treatment Phase
    STARTED 139
    COMPLETED 57
    NOT COMPLETED 82

    Baseline Characteristics

    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Overall Participants 294
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    40.3
    (12.4)
    Sex: Female, Male (Count of Participants)
    Female
    138
    46.9%
    Male
    156
    53.1%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment Response Based on Total PANSS Scale Score
    Description Response was defined as decrease of at least 30 percent in total Positive and Negative Syndrome Scale (PANSS) score from Baseline to endpoint of core phase (which is, Day 42 or early discontinuation). The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, & poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of sum of all 30 PANSS items & ranges from 30 to 210. Higher scores indicate worsening.
    Time Frame Day 42 or early discontinuation

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all participants who received at least one dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 294
    Number [Participants]
    195
    66.3%
    2. Secondary Outcome
    Title Change From Baseline in Total Positive and Negative Symptom Scale (PANSS) Score at Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least one dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement. "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 294
    Baseline (n=294)
    100.2
    (17.2)
    Change at Day 2 (n=294)
    -2.3
    (5.3)
    Change at Day 3 (n=287)
    -5.8
    (7.9)
    Change at Day 4 (n=288)
    -10.3
    (11.3)
    Change at Day 5 (n=284)
    -13.3
    (13.3)
    Change at Day 7 (n=286)
    -17.4
    (15.5)
    Change at Day 14 (n=276)
    -22.3
    (16.0)
    Change at Day 28 (n=254)
    -27.2
    (16.6)
    Change at Day 42 (n=234)
    -32.1
    (17.5)
    Change at Final Evaluation (n=294)
    -27.5
    (20.1)
    3. Secondary Outcome
    Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Day 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The PANSS is a 30-item scale to assess neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms and disorganized thoughts subscale, consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement (H/E) subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher score indicates greater severity. Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least one dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 294
    Positive Score: Baseline
    28.8
    (5.8)
    Positive Score: Change at Day 42
    -10.6
    (5.9)
    Positive Score: Change at Final Evaluation
    -9.1
    (6.7)
    Negative Score: Baseline
    24.8
    (6.1)
    Negative Score: Change at Day 42
    -6.5
    (5.1)
    Negative Score: Change at Final Evaluation
    -5.7
    (5.3)
    Disorganized Thoughts: Baseline
    23.4
    (4.9)
    Disorganized Thoughts: Change at Day 42
    -6.5
    (4.6)
    Disorganized Thoughts: Change at Final Evaluation
    -5.6
    (5.0)
    Uncontrolled H/E: Baseline
    10.6
    (3.7)
    Uncontrolled H/E: Change at Day 42
    -3.8
    (3.2)
    Uncontrolled H/E: Change at Final Evaluation
    -3.2
    (3.8)
    Anxiety/Depression: Baseline
    12.5
    (3.2)
    Anxiety/Depression: Change at Day 42
    -4.8
    (3.2)
    Anxiety/Depression: Change at Final Evaluation
    -3.9
    (3.7)
    4. Secondary Outcome
    Title Percentage of Participants With Treatment Response Greater Than (>) 20 Percent, 40 Percent and 50 Percent in Total Positive and Negative Syndrome Scale (PANSS) Score
    Description The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.
    Time Frame Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least one dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 294
    Treatment Response>20 Percent at Day 2
    4.4
    1.5%
    Treatment Response>20 Percent at Day 3
    12.9
    4.4%
    Treatment Response>20 Percent at Day 4
    29.9
    10.2%
    Treatment Response>20 percent at Day 5
    39.4
    13.4%
    Treatment Response>20 Percent at Day 7
    55.6
    18.9%
    Treatment Response>20 Percent at Day 14
    72.1
    24.5%
    Treatment Response>20 Percent at Day 28
    79.9
    27.2%
    Treatment Response>20 percent at Day 42
    87.6
    29.8%
    Treatment Response>20 Percent at Final Evaluation
    76.5
    26%
    Treatment Response>40 Percent at Day 2
    0
    0%
    Treatment Response>40 Percent at Day 3
    1.7
    0.6%
    Treatment Response>40 Percent at Day 4
    6.9
    2.3%
    Treatment Response>40 Percent at Day 5
    11.6
    3.9%
    Treatment Response>40 Percent at Day 7
    19.6
    6.7%
    Treatment Response>40 Percent at Day 14
    33.7
    11.5%
    Treatment Response>40 Percent at Day 28
    48.0
    16.3%
    Treatment Response>40 Percent at Day 42
    59.4
    20.2%
    Treatment Response>40 Percent at Final Evaluation
    51.4
    17.5%
    Treatment Response>50 Percent at Day 2
    0
    0%
    Treatment Response>50 Percent at Day 3
    0
    0%
    Treatment Response>50 Percent at Day 4
    2.8
    1%
    Treatment Response>50 Percent at Day 5
    7.4
    2.5%
    Treatment Response>50 Percent at Day 7
    11.2
    3.8%
    Treatment Response>50 Percent at Day 14
    18.1
    6.2%
    Treatment Response>50 Percent at Day 28
    29.9
    10.2%
    Treatment Response>50 Percent at Day 42
    41.5
    14.1%
    Treatment Response>50 Percent at Final Evaluation
    34.7
    11.8%
    5. Secondary Outcome
    Title Change From Baseline in Clinical Global Impression -Severity (CGI-S) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "normal, not at all ill" and a rating of 7 is equivalent to "among the most extremely ill participants". Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least 1 dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 289
    Baseline (n=289)
    3.9
    (0.7)
    Change at Day 7 (n=286)
    -0.6
    (0.7)
    Change at Day 14 (n=275)
    -0.9
    (0.8)
    Change at Day 28 (n=253)
    -1.2
    (0.9)
    Change at Day 42 (n=234)
    -1.5
    (0.9)
    Change at Final Evaluation (n=289)
    -1.2
    (1.0)
    6. Secondary Outcome
    Title Change From Baseline in Personal and Social Performance Scale (PSP) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The PSP assesses the degree of dysfunction within 4 domains of behavior: socially useful activities, personal & social relationships, self-care & disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 6, very severe) in each of 4 domains. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least 1 dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 290
    Baseline (n=290)
    50.0
    (14.3)
    Change at Day 7 (n=287)
    6.3
    (9.5)
    Change at Day 14 (n=276)
    9.9
    (10.5)
    Change at Day 28 (n=254)
    13.8
    (12.3)
    Change at Day 42 (n=235)
    16.1
    (13.9)
    Change at Final Evaluation (n=290)
    13.7
    (14.4)
    7. Secondary Outcome
    Title Change From Baseline in Quality of Sleep Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The sleep evaluation scale is a self-administered scale that rates quality of sleep. Participants indicate on an 11-point scale that how well they have slept within the previous 7 days, score ranged from 0 (very badly) to 10 (very well). Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least 1 dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 286
    Baseline (n=286)
    5.4
    (2.8)
    Change at Day 7 (n=280)
    1.4
    (2.9)
    Change at Day 14 (n=273)
    1.7
    (2.9)
    Change at Day 28 (n=250)
    2.1
    (3.0)
    Change at Day 42 (n=234)
    2.6
    (2.9)
    Change at Final Evaluation (n=286)
    2.1
    (3.2)
    8. Secondary Outcome
    Title Change From Baseline in Day Time Drowsiness Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The day time drowsiness evaluation scale is a self-administered scale that rates day time drowsiness. Participants indicate on an 11-point scale that how often they have felt drowsy within the previous 7 days, score ranged from 0 (not at all) to 10 (all the time). Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least 1 dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 286
    Baseline (n=286)
    3.4
    (2.7)
    Change at Day 7 (n=280)
    -0.5
    (2.5)
    Change at Day 14 (n=273)
    -1.0
    (2.6)
    Change at Day 28 (n=250)
    -1.4
    (2.7)
    Change at Day 42 (n=234)
    -1.6
    (2.6)
    Change at Final Evaluation (n=286)
    -1.4
    (2.7)
    9. Secondary Outcome
    Title Number of Participants Satisfied With the Study Treatment
    Description Treatment satisfaction with paliperidone ER was assessed by the Investigator and participant on a 5-point scale: 1 (very good), 2 (good), 3 (reasonable), 4 (moderate) and 5 (poor), at the end of the core treatment phase (which is, Day 42 or early discontinuation) by conducting an interview.
    Time Frame Day 42 or early discontinuation

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants who received at least 1 dose of paliperidone ER and provided at least 1 post-baseline efficacy measurement. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure at given time point.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 268
    Treatment efficacy: Very good
    66
    22.4%
    Treatment efficacy: Good
    111
    37.8%
    Treatment efficacy: Reasonable
    53
    18%
    Treatment efficacy: Moderate
    25
    8.5%
    Treatment efficacy: Poor
    13
    4.4%
    Treatment tolerability: Very good
    84
    28.6%
    Treatment tolerability: Good
    124
    42.2%
    Treatment tolerability: Reasonable
    35
    11.9%
    Treatment tolerability: Moderate
    15
    5.1%
    Treatment tolerability: Poor
    10
    3.4%
    10. Other Pre-specified Outcome
    Title Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The AIMS is a 12-item scale to provide a numeric measure to the observed abnormal movements in different parts of the body. Information is collected after a brief neurological examination and is scored on a 5-point scale (0=none and 4=severe). Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of paliperidone ER and had at least 1 post-baseline safety assessment. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 290
    Baseline (n=290)
    0.59
    (2.0)
    Change at Day 7 (n=287)
    -0.05
    (1.2)
    Change at Day 14 (n=276)
    -0.13
    (1.3)
    Change at Day 42 (n=234)
    -0.18
    (1.7)
    Change at Final Evaluation (n=290)
    -0.09
    (1.8)
    11. Other Pre-specified Outcome
    Title Change From Baseline in Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The SAS is a 10-item scale used to measure the symptoms of parkinsonism (slow movements) or parkinsonian side-effects related to the use of antipsychotic medications. The SAS rates 10 items (including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, Glabella tap, tremor and salivation), score ranging from 0 (normal) to 4 (extreme). The SAS global score is the average score (total sum of items score divided by the number of items) and ranges between 0 and 4, where the higher score indicates more severe condition of Extrapyramidal Symptoms. Final evaluation is the last post- baseline visit with data.
    Time Frame Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of paliperidone ER and had at least 1 post-baseline safety assessment. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 290
    Baseline (n=290)
    0.16
    (0.32)
    Change at Day 7 (n=287)
    0.00
    (0.23)
    Change at Day 14 (n=276)
    -0.00
    (0.24)
    Change at Day 42 (n=234)
    -0.02
    (0.24)
    Change at Final Evaluation (n=290)
    0.01
    (0.34)
    12. Other Pre-specified Outcome
    Title Change From Baseline in Global Rating Sub-scale Score Based on Barnes Akathisia Rating Scale (BARS) at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation)
    Description The BARS included an objective rating (from 0=normal to 3=constantly engaged), two subjective ratings of symptoms of akathisia, namely awareness of restlessness (ranging from 0=absence of inner restlessness to 3=awareness of intense compulsion to move) and reported distress related to restlessness (ranging from 0=no distress to 3=severe), and a global clinical rating of akathisia, ranging from 0 (absent) to 5 (severe). Global rating sub-scale score (that is, global clinical rating of akathisia) was assessed which was scored separately and is the most relevant measure of severity of akathisia. Higher scores indicates worsening akathisia. Final evaluation is the last post-baseline visit with data.
    Time Frame Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of paliperidone ER and had at least 1 post-baseline safety assessment. "N" (number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants who were evaluated for this measure at given time points.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    Measure Participants 290
    Baseline (n=290)
    0.17
    (0.5)
    Change at Day 7 (n=286)
    -0.02
    (0.4)
    Change at Day 14 (n=276)
    -0.01
    (0.5)
    Change at Day 42 (n=234)
    -0.03
    (0.5)
    Change at Final Evaluation (n=290)
    0.03
    (0.7)

    Adverse Events

    Time Frame 6 weeks in the core treatment phase
    Adverse Event Reporting Description An adverse event is any untoward medical occurrence in a clinical study participant administered with study treatment. It can be any unfavorable & unintended sign/abnormal finding, symptom, or disease temporally associated with use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
    Arm/Group Title Paliperidone Extended Release (ER)
    Arm/Group Description Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion was given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
    All Cause Mortality
    Paliperidone Extended Release (ER)
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Paliperidone Extended Release (ER)
    Affected / at Risk (%) # Events
    Total 23/294 (7.8%)
    Cardiac disorders
    Tachycardia 1/294 (0.3%)
    Gastrointestinal disorders
    Abdominal pain 1/294 (0.3%)
    General disorders
    Pyrexia 1/294 (0.3%)
    Injury, poisoning and procedural complications
    Alcohol poisoning 1/294 (0.3%)
    Nervous system disorders
    Extrapyramidal disorder 2/294 (0.7%)
    Mental impairment 1/294 (0.3%)
    Psychiatric disorders
    Acute psychosis 1/294 (0.3%)
    Anxiety 2/294 (0.7%)
    Depression 1/294 (0.3%)
    Insomnia 1/294 (0.3%)
    Intentional self-injury 1/294 (0.3%)
    Major depression 1/294 (0.3%)
    Schizophrenia 12/294 (4.1%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/294 (0.3%)
    Other (Not Including Serious) Adverse Events
    Paliperidone Extended Release (ER)
    Affected / at Risk (%) # Events
    Total 150/294 (51%)
    Cardiac disorders
    Tachycardia 25/294 (8.5%)
    Gastrointestinal disorders
    Constipation 9/294 (3.1%)
    Infections and infestations
    Nasopharyngitis 13/294 (4.4%)
    Nervous system disorders
    Akathisia 13/294 (4.4%)
    Extrapyramidal disorder 18/294 (6.1%)
    Headache 22/294 (7.5%)
    Psychiatric disorders
    Agitation 10/294 (3.4%)
    Anxiety 14/294 (4.8%)
    Insomnia 68/294 (23.1%)
    Restlessness 10/294 (3.4%)
    Sleep disorder 9/294 (3.1%)
    Vascular disorders
    Hypertension 13/294 (4.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title EMEA Therapeutic Area Leader CNS
    Organization Janssen-Cilag Germany
    Phone +492137955153
    Email
    Responsible Party:
    Janssen-Cilag International NV
    ClinicalTrials.gov Identifier:
    NCT00566631
    Other Study ID Numbers:
    • CR013162
    • R076477SCH3018
    First Posted:
    Dec 3, 2007
    Last Update Posted:
    Aug 2, 2013
    Last Verified:
    Jun 1, 2013